Antibodies specific for the L2C guinea pig leukemia were detected in sera of strain two guinea pigs that were protected against the leukemia after immunization with Ia+ (immune-associated antigen positive) L2C tumor cells. The protection lasted greater than 90 days from primary immunization. The syngeneic L2C antibodies were predominately of the IgGl isotype, specific for the L2C IgM idiotypic (Id) determinants, and of low affinity. Although the syngeneic anti-Id antibodies bound equally well to Ia+ and Ia- L2C tumor cells, the latter tumor subline was relatively ineffective in rendering tumor protection. These observations indicate that Ia antigens are probably important for the inductive but not necessarily for the effector phase of humoral immunity. In some of the protected guinea pigs that were subsequently hyperimmunized with Ia+ L2C tumor cells, cell-mediated reactivity against the L2C tumor cells was detected in the spleens. The effector cells were of the T-lymphocyte lineage and appeared to lack Fc-receptors. The specificity of the T-cytotoxic lymphocytes in vitro did not appear to be directed against the IgM Id determinants. These observations suggest that humoral and cell-mediated reactivity against the syngeneic L2C leukemia can be directed at different cell surface antigenic complexes. Initial experiments have shown that the passive administration of xenogeneic anti-Id antibodies to neonates and during their early development prolonged their survival to a lethal dose of leukemia cells compared to control animals. The increase in the survival time was dependent on the amount of anti-Id antibodies administered and was appreciably less than that achieved by immunization with Ia+ L2C tumor cells. (TA)